Segmenting and validating brain tissue definitions in the presence of varying tissue contrast

We assessed validity of the tissue definitions using synthetic brains and data for three large cohort of individuals with various neuropsychiatric disorders. Visual inspection and quantitative analyses showed that our method accurately and robustly defined the cortical mantle in brain images with varying contrast. Furthermore, associating the thickness with various demographic and clinical measures generated findings that were novel and supported by histological analyses or were supported by previous MRI studies, thereby validating the cortical definitions generated by the proposed method: (1) Although cortical thickness decreased with age in adolescents, in adults cortical thickness did not correlate significantly with age. Our synthetic data showed that the previously reported thinning of cortex in adults is likely due to decease in tissue contrast, thereby suggesting that the method generated cortical definitions in adults that were invariant to tissue contrast. In adolescents, cortical thinning with age was preserved likely due to widespread dendritic and synaptic pruning, even though the effects of decreasing tissue contrast were minimized. (3) The method generated novel finding of both localized increases and decreases in thickness of males compared to females after controlling for the differing brain sizes, which are supported by the histological analyses of brain tissue in males and females. (4) The proposed method, unlike prior methods, defined thicker cortex in BD individuals using lithium. The novel finding is supported by the studies that showed lithium treatment increased dendritic arborization and neurogenesis, thereby leading to thickening of cortex. (5) In both BD and ASD participants, associations of more severe symptoms with thinner cortex showed that correcting for the effects of tissue contrast preserved the biological consequences of illnesses. Therefore, consistency of the findings across the three large cohorts of participants, in images acquired on either 1.5T or 3T MRI scanners, and with findings from prior histological analyses provides strong evidence that the proposed method generated valid and accurate definitions of the cortex while controlling for the effects of tissue contrast.